This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a Phase I study of IMC-A12 (Imclone Systems), a recombinant human monoclonal antibody to the insulin-like growth factor-I receptor (IGF-IR), in pediatric patients with recurrent/refractory solid tumors. The insulin-like growth factor (IGF)system plays a critical role in the development and progression of many types of cancer,including many pediatric-specific cancers. IGF-I and IGF-II ligand signaling through the IGF-IR transmembrane tyrosine kinase promotes cancer cell proliferation and survival. Use of monoclonal antibodies to disrupt IGF-IR signaling has shown anti-tumor activity in a variety of cancers in vitro, in animal models, and in early-phase adult trials. In this Phase I trial, we will evaluate the toxicity profile and determine the maximum tolerated dose (MTD) of IMC-A12 administered intravenously on a once a week schedule in children and adolescents with relapsed or refractory solid tumors. Patients aged 1-21 years with refractory solid tumors will be enrolled in a standard Phase I dose escalation trial at a starting dose of 6 mg/kg. The study will include one dose escalation up to 9 mg/kg and potential dose de-escalation if IMC-A12 is not found to be tolerable in children at the 6 mg/kg dose. Due to clinical evidence of anti-tumor activity for IGF-1R inhibitors in patients with Ewing sarcoma/peripheral PNET, a separate stratum that includes patients with this diagnosis has been incorporated in this trial. Patients in the Ewing sarcoma/peripheral PNET stratum will accrue at a dose level that has been found to be tolerable in the solid tumor stratum. The pharmacokinetics of IMC-A12 in children will also be evaluated in this study. Correlative biology studies will include assessment of IGF-IR and insulin receptor (IR) expression and activation in peripheral blood mononuclear cells. Circulating levels of IGF-I, IGF-II, IGF-BP3, growth hormone, insulin, and C-peptide will be measured preand post-treatment with IMC-A12. Tumor tissue, when available, will be obtained and banked for future studies. IMC-A12 will have anti-tumor activity in children with relapsed/refractory solid tumors. Primary Aims 1. To estimate the maximum tolerated dose (MTD) or recommended dose for Phase 2 evaluation of IMC-A12 administered as an IV infusion once weekly in children with relapsed/refractory solid tumors using a limited dose escalation strategy.